异鼠李素通过调控NF-κB通路发挥镇痛作用

杨宇; 胥学冰; 蒋殿宇; 佟杰; 郭大为; 林琳

doi:10.16016/j.1000-5404.202101133

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异鼠李素通过调控NF-κB通路发挥镇痛作用

基础医学 | 更新时间：2026-01-09

- 异鼠李素通过调控NF-κB通路发挥镇痛作用
- Isorhamnetin plays an analgesic role by regulating NF-κB pathway
- 第三军医大学学报 2021年43卷第14期页码：1366-1371
- 作者机构：
  
  1.110034 沈阳，武警辽宁省总队医院麻醉科
  2.110032 沈阳，辽宁中医药大学附属医院麻醉科
  3.110013 沈阳，沈阳市红十字会医院药剂科
  4.110001 沈阳，沈阳市肛肠医院麻醉科
- 作者简介：
  
  [ 胥学冰，E-mail: 985929004@qq.com XU Xuebing, E-mail: 985929004@qq.com
- 基金信息：
- DOI：10.16016/j.1000-5404.202101133
  中图分类号： R282.71;R966;R971.1
- 收稿：2021-01-15，
  
  修回：2021-03-30，
  
  纸质出版：2021-07-30
- 稿件说明：
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杨宇, 胥学冰, 蒋殿宇, 等. 异鼠李素通过调控NF-κB通路发挥镇痛作用[J]. 第三军医大学学报, 2021,43(14):1366-1371.

Yu YANG, Xuebing XU, Dianyu JIANG, et al. Isorhamnetin plays an analgesic role by regulating NF-κB pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1366-1371.
杨宇, 胥学冰, 蒋殿宇, 等. 异鼠李素通过调控NF-κB通路发挥镇痛作用[J]. 第三军医大学学报, 2021,43(14):1366-1371. DOI： 10.16016/j.1000-5404.202101133.

Yu YANG, Xuebing XU, Dianyu JIANG, et al. Isorhamnetin plays an analgesic role by regulating NF-κB pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1366-1371. DOI： 10.16016/j.1000-5404.202101133.

摘要

目的

研究异鼠李素的镇痛作用及潜在机制。

方法

采用小鼠热板致痛模型和小鼠醋酸扭体疼痛模型研究异鼠李素的镇痛作用。每种模型需选取50只SPF级昆明种小鼠，依据体质量分为5组，分别为空白对照组，阳性对照吲哚美辛组，异鼠李素高、中、低剂量组。Griess法和酶联免疫法检测小鼠免疫细胞RAW264.7中一氧化氮(NO)和肿瘤坏死因子(TNF-α)含量；RT-PCR法检测IL-1β和IL-6表达水平；Western blot检测NF-κB信号通路的变化。

结果

在体动物实验表明异鼠李素(25

100 mg/kg)可以剂量依赖性地提高小鼠对热板所致疼痛的痛阈值(

0.05)，并可显著减少醋酸所致的小鼠扭体数(

0.05)。体外细胞实验表明异鼠李素(5，10，20 μmol/L)显著抑制脂多糖(LPS)诱导的RAW264.7细胞中NO和TNF-α含量升高(

0.05)，降低IL-1β和IL-6的mRNA表达水平，并可以阻断RAW264.7细胞NF-κB信号通路的激活。预先给予NF-κB信号通路抑制剂可以与异鼠李素协同调节RAW264.7细胞NO的水平。

结论

异鼠李素具有一定的镇痛作用，其镇痛机制可能与抑制NF-κB通路，继而减少NO、TNF-α、IL-1及IL-6的表达、合成或释放有关。

Abstract

Objective

To investigate the analgesic effect of isorhamnetin and its underlying mechanisms.

Methods

The analgesic effect of isorhamnetin was measured by hot plate pain model and acetic acid torsion pain model in mice. Fifty SPF Kunming mice were selected in each model and then were randomly divided into 5 groups according to their body weight: blank control group

positive control indomethacin group

and isorhamnetin high

middle and low dose groups

and the analgesic effect of isorhamnetin was observed and recorded. In addition

the effects of isorhamnetin on the expression levels of pain-inducing factors and inflammatory factors were examined. The contents of NO and TNF-α in mouse macrophage RAW264.7 cells were detected by Griess assay and ELISA assay

respectively

and the mRNA levels of IL-1β and IL-6 in RAW264.7 cells were determined using RT-PCR. Finally

the activation of NF-κB pathway in LPS-induced RAW264.7 was determined by Western blotting.

Results

In vivo

experiments showed that isorhamnetin (25

50 and 100 mg/kg) dose-depend

ently increased the pain threshold of mice induced by hot plate test (

0.05)

and significantly reduced the acetic acid-induced writhing response in mice (

0.05).

In vitro

cell experiments suggested that isorhamnetin (5

20 μmol/L) greatly inhibited the up-regulation of NO and TNF-α induced by LPS (

0.05)

decreased the mRNA levels of IL-1β and IL-6

and blocked the activation of NF-κB signaling pathway in RAW264.7 cells. Pre-administration of the inhibitor of NF-κB pathway synergically enhanced the inhibitory effect of isorhamnetin on NO level in RAW264.7 cells.

Conclusion

Isorhamnetin has certain analgesic effect

and its mechanism may be associated with the suppression of NF-κB pathway and the subsequent reductions in expression

syntheses and releases of NO

TNF-α

IL-1β and IL-6.

关键词

Keywords

references

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